Soham Maity

Oxidative Trifluoromethylation of Unactivated Olefins: An Efficient and Practical Synthesis of α-Trifluoromethyl-Substituted Ketones†

The incorporation of a CF3 group in a compound of pharmacological relevance usually results in significant enhancement of its lipophilicity, binding selectivity, and metabolic stability. A number of highly effective methods for the incorporation of a CF3 moiety into commonly used synthetic scaffolds have been reported. In this context, the synthesis of a-CF3-substituted carbonyl compounds [10–14] has recently drawn significant attention, owing to their importance for both pharmaceutical and synthetic research. Generally, a-CF3-substituted carbonyl compounds are prepared from silyl enol ethers and enolates by using various radical and electrophilic trifluoromethylating agents (Scheme 1). Strong bases, such as lithium diisopropylamide (LDA), are often employed in the synthesis of these precursors, thus limiting the available methods by extra

Remote para-C–H Functionalization of Arenes by a D-Shaped Biphenyl Template-Based Assembly

Site-selective C-H functionalization has emerged as an efficient tool in simplifying the synthesis of complex molecules. Most often, directing group (DG)-assisted metallacycle formation serves as an efficient strategy to ensure promising regioselectivity. A wide variety of ortho- and meta-C-H functionalizations stand as examples in this regard. Yet despite this significant progress, DG-assisted selective para-C-H functionalization in arenes has remained unexplored, mainly because it involves the formation of a geometrically constrained metallacyclic transition state. Here we report an easily recyclable, novel Si-containing biphenyl-based template that directs efficient functionalization of the distal p-C-H bond of toluene by forming a D-shaped assembly. This DG allows the required flexibility to support the formation of an oversized pre-transition state. By overcoming electronic and steric bias, para-olefination and acetoxylation were successfully performed while undermining o- and m-C-H activation. The applicability of this D-shaped biphenyl template-based strategy is demonstrated by synthesizing various complex molecules.

Efficient and Stereoselective Nitration of Mono- and Disubstituted Olefins with AgNO2 and TEMPO

Nitroolefin is a common and versatile reagent. Its synthesis from olefin is generally limited by the formation of mixture of cis and trans compounds. Here we report that silver nitrite (AgNO2) along with TEMPO can promote the regio- and stereoselective nitration of a broad range of olefins. This work discloses a new and efficient approach wherein starting from olefin, nitroalkane radical formation and subsequent transformations lead to the desired nitroolefin in a stereoselective manner.

Stereoselective Nitration of Olefins with tBuONO and TEMPO: Direct Access to Nitroolefins under Metal-free Conditions

Nitroolefins are essential elements for both synthetic chemistry and medicinal research. Despite significant improvements in nitration of olefin an efficient metal-free synthesis remains elusive so far. Herein, we disclose a new set of reagents to access nitroolefins in a single step under metal-free conditions. A wide range of olefins with diverse functionalities has been nitrated in synthetically useful yields. This transformation is operationally simple and exhibits excellent E-selectivity. Furthermore, site selective nitration in a complex setup makes this method advantageous.

A general and efficient aldehyde decarbonylation reaction by using a palladium catalyst

A facile decarbonylation reaction of aldehydes has been developed by employing Pd(OAc)(2). A wide variety of substrates are decarbonylated, without using any exogenous ligand for palladium as well as CO-scavenger.

ipso-Nitration of arylboronic acids with bismuth nitrate and perdisulfate.

An efficient and one pot synthetic method of ipso-nitration of arylboronic acids has been developed. The high efficiency, general applicability, and broader substrate scope including heterocycles and functional groups make this method advantageous. Due to its simplicity, we expect to find application of this method in synthesis.

A predictably selective nitration of olefin with Fe(NO3)3 and TEMPO.

Ferric nitrate with catalytic TEMPO has been identified as a useful reagent for regio- and stereoselective nitration of a wide variety of aromatic, aliphatic, and heteroaromatic olefins. This reaction provided nitroolefins in preparatively useful yields with excellent E-selectivity. Due to its mild nature and operational simplicity, the present protocol is expected to find application in synthetic setup.

Aerobic Oxynitration of Alkynes with tBuONO and TEMPO

An efficient method for stereoselective nitroaminoxylation of alkyne has been reported. The reaction enjoys a broad substrate scope, good functional group tolerance, and high yields. Synthetically useful α-nitroketones can be accessed through these products in a single step.

Predictably Selective (sp3)C–O Bond Formation through Copper Catalyzed Dehydrogenative Coupling: Facile Synthesis of Dihydro-oxazinone Derivatives

An intramolecular dehydrogenative (sp(3))C-O bond formation in salicylamides can be initiated by an active Cu/O2 species to generate pharamaceutically relevant dihydro-oxazinones. Experimental findings suggest that stereoelectronic parameters in both coupling partners are controlling factors for site selectivity in bond formation. Mechanistic investigations including isotope labeling, kinetic studies helped to propose a catalytic cycle. The method provides a convenient synthesis of an investigational new medicine CX-614, which has potential in finding treatment for Parkinsons and Alzheimers diseases.

Nickel‐Catalyzed Insertion of Alkynes and Electron‐Deficient Olefins into Unactivated sp3 CH Bonds

Insertion of unsaturated systems such as alkynes and olefins into unactivated sp(3) C-H bonds remains an unexplored problem. We herein address this issue by successfully incorporating a wide variety of functionalized alkynes and electron-deficient olefins into the unactivated sp(3) C-H bond of pivalic acid derivatives with excellent syn- and linear- selectivity. A strongly chelating 8-aminoquinoline directing group proved beneficial for these insertion reactions, while an air-stable and inexpensive Ni(II) salt has been employed as the active catalyst.